Prostaglandins (PGs) signal diverse biological processes in the kidney. This proposal concerns itself with several fundamental aspects of paracrine PG signaling in the glomerulus. PGs cannot enter, let alone traverse, a cell without a carrier. Our lab has extensively characterized PGT, a lactate/PG antiporter that mediates the energetically-active uptake of PGs into cells. This application builds on the observation that PGT is expressed in aortic, arteriolar, glomerular, and venular endothelial cells. We hypothesize that PGT is expressed at the glomerular endothelial luminal membrane where it translocates PGE2 from the vascular lumen toward podocytes, and that the resulting stimulation of podocytes by PGs modifies its biological response to other stimuli, especially TGF-beta. Our Specific Aims are to test the following hypotheses: 1. Cultured rat aortic endothelial cells (RAECs), human microvascular endothelial cells (hMVECs), and bovine and murine glomerular endothelial cells (GEnCs) express luminal PGT and engage in PG transport and directional release of PGs via sided reuptake. 2. Hypoxia, TGF-beta, and/or IL-1beta regulate PGT in RAECs, hMVECs, and GEnCs by supplying more lactate for PG reuptake and/or by altering luminal plasma membrane PGT expression. 3. PGs modulate podocyte apoptosis in response to TGF-beta in vitro. 4. Disease-modifier genes in podocytes are transcriptionally regulated by PGs and can be discovered using a DNA microarray approach.